Abstract
Our previous studies have demonstrated overexpression of Mcl-1 in cervical cancer tumorigenesis. However, the molecular mechanism of its overexpression remains not elucidated. MiR-320 has been reported to be down-regulated in various types of cancer, and bioinformatics prediction indicated that it may regulate the expression of Mcl-1. The aim of this study is to investigate the role of miR-320 and its target gene Mcl-1 in cervical cancer progression and to assess their clinical significance. miR-320 and Mcl-1 expressions in human cervical cancer tissues were investigated by qRT-PCR, in situ hybridization, and immunohistochemical staining, respectively. The clinicopathological implications of these molecules were analyzed. Bioinformatic prediction and luciferase assays were employed to identify the predicted microRNA (miRNA) which regulates Mcl-1. The apoptosis, proliferation, migration, and invasion assays were performed to investigate the effect of miR-320 on the cervical cancer cells. MiR-320 expression is significantly down-regulated versus Mcl-1 expression is up-regulated in cervical cancer tissues compared with normal controls with a negative correlation between them. Luciferase assay showed that miR-320 negatively regulates Mcl-1 expression. In addition, miR-320 induces apoptosis via down-regulation of Mcl-1 and activation of caspase-3 but inhibits cell proliferation, migration, invasion, and tumorigenesis in cervical cancer cells. Our studies show that miR-320 expression is decreased in cervical cancer, and its expression is negatively correlated with Mcl-1 expression in cervical cancer. In addition, miR-320 inhibits cervical cancer progression by down-regulation of Mcl-1. These results indicate that miR-320 may be an important biomarker and target for diagnosis and treatment of cervical cancer patient.
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Acknowledgments
This work was supported by the National Natural Science Foundation of China (81202043 and 81372480), the Postdoctorate Foundation of Jiangsu Province (1401017A), the Postdoctorate Foundation of China (2014M560437 and 2015T80570), the Six Talent Peaks Project Foundation of Jiangsu Province (2014-WSW-059) and the Foundation of Wuxi City Health and Family Planning (MS201501). Authors thank all the women who donated tissues for this study.
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Zhang, T., Zou, P., Wang, T. et al. Down-regulation of miR-320 associated with cancer progression and cell apoptosis via targeting Mcl-1 in cervical cancer. Tumor Biol. 37, 8931–8940 (2016). https://doi.org/10.1007/s13277-015-4771-6
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DOI: https://doi.org/10.1007/s13277-015-4771-6